Abstract
Tuberculosis (TB) remains a public health crisis, requiring the urgent identification of new anti-mycobacterial drugs. We screened several organic and aqueous marine invertebrate extracts for their in vitro inhibitory activity against the causative organism, Mycobacterium tuberculosis. Here, we report the results obtained for 54 marine invertebrate extracts. The chemical components of two of the extracts were dereplicated, using 1H NMR and HR-LCMS with GNPS molecular networking, and these extracts were further subjected to an activity-guided isolation process to purify the bioactive components. Hyrtios reticulatus yielded heteronemin 1 and Jaspis splendens was found to produce the bengamide class of compounds, of which bengamides P 2 and Q 3 were isolated, while a new derivative, bengamide S 5, was putatively identified and its structure predicted, based on the similarity of its MS/MS fragmentation pattern to those of other bengamides. The isolated bioactive metabolites and semi-pure fractions exhibited M. tuberculosis growth inhibitory activity, in the range <0.24 to 62.50 µg/mL. This study establishes the bengamides as potent antitubercular compounds, with the first report of whole-cell antitubercular activity of bengamides P 2 and Q 3.
Highlights
Tuberculosis (TB), which is caused by Mycobacterium tuberculosis (Mtb), remains a leading cause of death, globally
An initial set of 984 organic and aqueous marine invertebrate extracts were screened for their in vitro inhibitory activity against a fully virulent M. tuberculosis H37Rv fluorescent reporter mutant [16,18,19] and the minimum inhibitory concentrations required to inhibit 90% (MIC90 ) and 99% (MIC99 ) of the mycobacterial population were recorded
Marine-natural products are a reliable source of potent antitubercular leads, as this screening project identified 54 actives in whole-cell growth inhibition assays
Summary
Tuberculosis (TB), which is caused by Mycobacterium tuberculosis (Mtb), remains a leading cause of death, globally. Despite the availability of an effective anti-TB chemotherapy and a neonatal vaccine, an estimated 10 million people contracted TB and 1.4 million people died of the disease, globally, in 2019 [1]. Delayed diagnosis, inappropriate treatment and non-adherence has led to the emergence of multidrugresistant (MDR) and extensively drug-resistant (XDR) Mtb strains [1,3]. Treatment of these resistant strains requires the use of non-frontline drugs, often over prolonged periods and with associated risks, including severe side effects and high therapeutic cost [3,4,5]. There is, an urgent need to discover and develop new potent anti-TB drugs with reduced side effects and effectiveness over shorter periods
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
